The aim of this study was to examine the impact of the most prevalent comorbid chronic diseases in hypertensives on health-related quality of life (HRQOL) in the general representative Korean population using the EuroQOL-5D (EQ-5D) and to assess this impact by sex and after controlling for sociodemographic factors. The effects of hypertension and comorbidity on HRQOL were examined using multiple linear regression models with Fourth Korean National Health and Nutrition Examination Survey data. In a total of 5736 adults, the prevalence of hypertension alone was 20.8%, and the prevalence rates of hypertension comorbid with diabetes mellitus (DM), cardiovascular disease (CVD), and musculoskeletal (MS) disease were 9.5%, 3.8%, and 33.5%, respectively. Females with hypertension and other comorbidity showed worse HRQOL scores, with the exception of hypertension and CVD, where males scored worse for HRQOL. After adjustment, subjects with comorbid DM, CVD, or MS experienced EQ-5D scores decreasing by 0.01, 0.09, and 0.05, respectively. Since comorbidity impairs HRQOL in hypertensives, health providers should consider comorbid diseases in hypertensives when developing methods of intervention to effectively manage hypertension.